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The synthetic estrogen diethylstilbestrol (DES) inhibits the telomerase activity and gene expression of prostate cancer cells
Author(s) -
Geier Rinat,
Adler Shulamit,
Rashid Gloria,
Klein Ami
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21166
Subject(s) - lncap , telomerase , dihydrotestosterone , prostate cancer , androgen , endocrinology , medicine , testosterone (patch) , cancer research , biology , estrogen , diethylstilbestrol , cancer , hormone , gene , biochemistry
BACKGROUND Telomerase, which lengthens telomeres, is normally down‐regulated in somatic cells and highly up‐regulated in dividing cells, such as malignant cells. Human prostate cancer is androgen dependent. Estrogens, including the synthetic estrogen diethylstilbestrol (DES), are used in prostate cancer treatment to reduce androgen levels via feedback inhibition of the hypothalamic release of luteinizing hormone releasing hormone (LH‐RH). DES has also direct anticancer activities, such as apoptosis induction. We investigated in vitro the effect of DES on telomerase activity and on gene expression in the presence and absence of androgens. We used two prostate cancer cell lines: LNCaP (androgen dependent) and PC3 (androgen independent). METHODS LNCaP and PC3 cells were treated with 0.1–1,000 nM testosterone or dihydrotestosterone (DHT) in the presence of DES (25 or 50 µM). Cell telomerase activity and gene expression (mRNA) were measured. RESULTS LNCaP : As expected, testosterone and DHT significantly increased telomerase activity and gene expression. However, these effects were inhibited by DES. Contrary to expectations, the combination of DES and testosterone functioned synergistically leading to complete inhibition of telomerase activity. PC3 : Testosterone and DHT did not affect telomerase activity and gene expression, whereas DES, in the absence or presence of the androgens, significantly inhibited telomerase activity. CONCLUSIONS In the present study, we demonstrated the ability of DES to inhibit telomerase in prostate cancer cells. Androgens did not limit the inhibitory effect and even acted synergistically with DES in the LNCaP line. This phenomenon should be considered if telomerase inhibition is part of prostate cancer treatment. Prostate 70:1307–1312, 2010. © 2010 Wiley‐Liss, Inc.